Immune infiltration, aggressive pathology, and poor survival outcomes in RECQL helicase deficient breast cancers

Ayat Lashen; Abdulbaqi Al-Kawaz; Jennie N Jeyapalan; Shatha Alqahtani; Ahmed Shoqafi; Mashael Algethami; Michael Toss; Andrew R Green; Nigel P Mongan; Sudha Sharma; Mohammad R Akbari; Emad A Rakha; Srinivasan Madhusudan

Neoplasia: An International Journal for Oncology Research (Jan 2024)

Immune infiltration, aggressive pathology, and poor survival outcomes in RECQL helicase deficient breast cancers

Ayat Lashen,
Abdulbaqi Al-Kawaz,
Jennie N Jeyapalan,
Shatha Alqahtani,
Ahmed Shoqafi,
Mashael Algethami,
Michael Toss,
Andrew R Green,
Nigel P Mongan,
Sudha Sharma,
Mohammad R Akbari,
Emad A Rakha,
Srinivasan Madhusudan

Affiliations

Ayat Lashen: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK
Abdulbaqi Al-Kawaz: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; Department of Pathology, Nottingham University Hospital, City Campus, Hucknall Road, Nottingham NG51PB, UK.
Jennie N Jeyapalan: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK
Shatha Alqahtani: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK
Ahmed Shoqafi: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK
Mashael Algethami: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK
Michael Toss: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; Department of Pathology, Nottingham University Hospital, City Campus, Hucknall Road, Nottingham NG51PB, UK.
Andrew R Green: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK
Nigel P Mongan: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA
Sudha Sharma: Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street, NW, Washington, DC 20059, USA
Mohammad R Akbari: Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto. Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
Emad A Rakha: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; Department of Pathology, Nottingham University Hospital, City Campus, Hucknall Road, Nottingham NG51PB, UK.
Srinivasan Madhusudan: Nottingham Breast Cancer Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; Department of Oncology, Nottingham University Hospitals, Nottingham NG51PB, UK; Corresponding author at: Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK.

Journal volume & issue: Vol. 47
p. 100957

Abstract

Read online

RECQL is essential for genomic stability. Here, we evaluated RECQL in 449 pure ductal carcinomas in situ (DCIS), 152 DCIS components of mixed DCIS/invasive breast cancer (IBC) tumors, 157 IBC components of mixed DCIS/IBC and 50 normal epithelial terminal ductal lobular units (TDLUs). In 726 IBCs, CD8+, FOXP3+, IL17+, PDL1+, PD1+ T-cell infiltration (TILs) were investigated in RECQL deficient and proficient cancers. Tumor mutation burden (TMB) was evaluated in five RECQL germ-line mutation carriers with IBC by genome sequencing. Compared with normal epithelial cells, a striking reduction in nuclear RECQL in DCIS was evident with aggressive pathology and poor survival. In RECQL deficient IBCs, CD8+, FOXP3+, IL17+ or PDL1+ TILs were linked with aggressive pathology and shorter survival. In germline RECQL mutation carriers, increased TMB was observed in 4/5 tumors. We conclude that RECQL loss is an early event in breast cancer and promote immune cell infiltration.

Published in Neoplasia: An International Journal for Oncology Research

ISSN: 1522-8002 (Print); 1476-5586 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/neoplasia/

About the journal

Abstract

Keywords